@article{46cec51eb80b47e5adb751b380469b1c,
title = "Midcourse correction to a clinical trial when the event rate is underestimated: The Look AHEAD (Action for Health in Diabetes) Study",
abstract = "The Look AHEAD (Action for Health in Diabetes) Study is a long-term clinical trial that aims to determine the cardiovascular disease (CVD) benefits of an intensive lifestyle intervention (ILI) in obese adults with type 2 diabetes. The study was designed to have 90% statistical power to detect an 18% reduction in the CVD event rate in the ILI Group compared to the Diabetes Support and Education (DSE) Group over 10.5 years of follow-up. The original power calculations were based on an expected CVD rate of 3.125% per year in the DSE group; however, a much lower-than-expected rate in the first 2 years of follow-up prompted the Data and Safety Monitoring Board (DSMB) to recommend that the Steering Committee undertake a formal blinded evaluation of these design considerations. The Steering Committee created an Endpoint Working Group (EPWG) that consisted of individuals masked to study data to examine relevant issues. The EPWG considered two primary options: (1) expanding the definition of the primary endpoint and (2) extending follow-up of participants. Ultimately, the EPWG recommended that the Look AHEAD Steering Committee approve both strategies. The DSMB accepted these modifications, rather than recommending that the trial continue with inadequate statistical power. Trialists sometimes need to modify endpoints after launch. This decision should be well justified and should be made by individuals who are fully masked to interim results that could introduce bias. This article describes this process in the Look AHEAD study and places it in the context of recent articles on endpoint modification and recent trials that reported endpoint modification.",
author = "Brancati, {Frederick L.} and Mary Evans and Furberg, {Curt D.} and Nancy Geller and Steven Haffner and Kahn, {Steven E.} and Kaufmann, {Peter G.} and Lewis, {Cora E.} and Nathan, {David M.} and Bertram Pitt and Safford, {Monika M.}",
note = "Funding Information: This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women{\textquoteright}s Health; the Centers for Disease Control and Prevention; and the Department of Veterans Affairs. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of the IHS or other funding sources. Funding Information: Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719) and the Prevention & Control Core of the Baltimore Diabetes Research & Training Center (P60KD079637); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (GCRC) (M01RR000056), the Clinical Translational Research Center (CTRC) funded by the Clinical & Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); and the Frederic C. Bartter General Clinical Research Center (M01RR01346) ",
year = "2012",
month = feb,
doi = "10.1177/1740774511432726",
language = "English (US)",
volume = "9",
pages = "113--124",
journal = "Clinical Trials",
issn = "1740-7745",
publisher = "SAGE Publications Ltd",
number = "1",
}